Management Approaches and Patient Outcomes for Giant Pituitary Neuroendocrine Tumors Classified as Knosp Grade 3 and 4.

Background Treatment of patients with a giant pituitary neuroendocrine tumor (GPitNET) is challenging. Here, we present the methods used for the clinical management of patients who underwent GPitNET resection mainly via endoscopic endonasal surgery along with multimodal support to avoid surgical complications, which can affect the outcomes. Methodology The medical records of 25 patients with a GPitNET who underwent endonasal endoscopic surgery were retrospectively reviewed. Complications were analyzed and factors affecting the extent of resection were evaluated. Results Gross total resection was achieved in six (24%), near-total resection (>90%) in nine (36%), and partial resection in 10 (40%) patients. Multivariate analyses revealed that tumors invading the middle fossa had negative effects on the extent of resection (odds ratio = 0.092, p = 0.047). Postoperative vision improved or normalized in 16 (64%), remained stable in eight (32%), and worsened in one (4%), while a new hormonal deficit was noted in seven (28%) patients. Complications included permanent oculomotor nerve palsy in one (4%) and transient oculomotor palsy in one (4%), apoplexy of the residual tumor resulting in ischemic stroke in one (4%), postoperative cerebrospinal fluid leakage in one (4%), and permanent diabetes insipidus in six (24%) patients. Conclusions For GPitNETs that extend into the middle fossa, our study underscored the difficulties in surgical extraction and the necessity for tailored treatment approaches. To ensure the safest and most complete removal possible, the surgical strategy must be specifically adapted to each case. Additionally, employing a comprehensive support approach is essential to reduce the chance of complications in patients impacted by this condition.

Intraoperative monitoring of trigeminal neuralgia: a technical note.

Trigeminal neuralgia causes excruciating pain in patients. Microvascular decompression is indicated for drug-resistant s trigeminal neuralgia. Unlike facial spasms, any part of the nerve can be the culprit, not only the root entry zone. Intraoperative monitoring does not yet exist for trigeminal neuralgia. We successfully used intermittent stimulation of the superior cerebellar artery during surgery and confirmed the disappearance of the trigeminal nerve motor branch reaction after the release of the compression. Intermittent direct stimulation of the culprit blood vessel using the motor branch of the trigeminal nerve may assist in intraoperative monitoring of decompression during trigeminal nerve vascular decompression surgery.

Pre-treatment systemic inflammation response index and systemic immune inflammation in patients with primary central nerve system lymphoma as a useful prognostic indicator.

PURPOSE: The systemic inflammation response index (SIRI) and systemic immune-inflammation index (SII) are based on neutrophil, monocyte, platelet, and lymphocyte counts. The SIRI and SII are used to predict the survival of patients with malignant tumors. It is well known that the inflammatory immune response is closely related to cancer occurrence and progression. In the present study, we evaluated the potential prognostic significance of SIRI and SII in patients with primary central nervous system lymphoma (PCNSL). METHODS: Fifty-eight consecutive patients were enrolled in this study between November 2006 and May 2022. Among the 58 patients, 47 patients with sufficient blood test data and follow-up were analyzed. The patients with steroid intake at the time point of the blood test and higher C-reactive protein were excluded. RESULTS: The median follow-up and survival times were 31 and 36 months, respectively. The optimal cutoff SIRI value was based on the receiver operating characteristic curve (ROC) for overall survival (OS) and stratified patients into low (< 1.43 × 109/L, n = 22) and high (≥ 1.43 × 109/L, n = 25) SIRI groups. The optimal cutoff SII value based on the ROC for OS stratified patients into low (< 694.9, n = 28) and high (≥ 694.9, n = 19) SII groups. A low SIRI value was associated with longer OS (p = 0.006). Furthermore, a low SII value was associated with longer OS (p = 0.044). The prognostic factors associated with prolonged survival in univariate analysis using the Cox proportional hazard model were age < 65 years, low SIRI, and low SII. The multivariate analysis demonstrated that age < 65 years and low SIRI independently predicted longer OS. CONCLUSION: Simple, less expensive, and routinely ordered preoperative blood count assessments such as SIRI and SII predict the OS of patients with PCNSL. This study demonstrated that PCNSL is associated with pre-treatment systemic immune-inflammation states.

Preoperative Blood Counts Predict Overall Survival in Patients Undergoing Surgical Removal of Brain Metastasis.

OBJECTIVE: The prognosis for patients with cancer with brain metastasis (BM) requiring surgical removal is quite limited. Preoperative prognostic factors can provide meaningful information to surgeons, oncologists, and patients. This study evaluated the preoperative blood counts in patients with BM who were treated with surgical removal. METHODS: Between January 2011 and November 2021, 221 consecutive surgeries were conducted on 198 patients with BM. Among the 198 patients, 188 patients with sufficient blood test data and follow-up were analyzed in this study. The tumors originated from the lungs (n = 102, 54.3%), colon (n = 26, 13.3%), breast (n = 13, 6.9%), kidney (n = 8, 4.3%), stomach (n = 6, 3.2%), and others (n = 33, 17.6%). The blood test data included neutrophils, lymphocytes, monocytes, eosinophils, basophils, red blood cell count, hemoglobin, and albumin. RESULTS: The median follow-up and median survival times were both 11 months (range: 0-139 months). Higher neutrophil-lymphocyte ratio ≥ 3.17, platelet-lymphocyte ratio ≥112.7, systemic immune-inflammation index ≥594.4, systemic inflammation response index ≥1.25 were unfavorable predictors of prognosis for the patients treated with surgical removal for BM (P < 0.001). Furthermore, lower lymphocyte-monocyte ratio < 2.33 and prognostic nutritional index < 48.5 were unfavorable predictors. CONCLUSIONS: Simple, less expensive, routinely ordered preoperative blood count assessments, such as the neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, lymphocyte-monocyte ratio, systemic immune-inflammation index, systemic inflammation response index, and prognostic nutritional index, can predict the overall survival of patients treated with surgical removal for BM.

Antitumor Effects of Intravenous Natural Killer Cell Infusion in an Orthotopic Glioblastoma Xenograft Murine Model and Gene Expression Profile Analysis.

Despite standard multimodality treatment, containing maximum safety resection, temozolomide, radiotherapy, and a tumor-treating field, patients with glioblastoma (GBM) present with a dismal prognosis. Natural killer cell (NKC)-based immunotherapy would play a critical role in GBM treatment. We have previously reported highly activated and ex vivo expanded NK cells derived from human peripheral blood, which exhibited anti-tumor effect against GBM cells. Here, we performed preclinical evaluation of the NK cells using an in vivo orthotopic xenograft model, the U87MG cell-derived brain tumor in NOD/Shi-scid, IL-2RɤKO (NOG) mouse. In the orthotopic xenograft model, the retro-orbital venous injection of NK cells prolonged overall survival of the NOG mouse, indirectly indicating the growth-inhibition effect of NK cells. In addition, we comprehensively summarized the differentially expressed genes, especially focusing on the expression of the NKC-activating receptors' ligands, inhibitory receptors' ligands, chemokines, and chemokine receptors, between murine brain tumor treated with NKCs and with no agents, by using microarray. Furthermore, we also performed differentially expressed gene analysis between an internal and external brain tumor in the orthotopic xenograft model. Our findings could provide pivotal information for the NK-cell-based immunotherapy for patients with GBM.

Bulk RNA sequencing reveals the comprehensive genetic characteristics of human cord blood-derived natural killer cells.

Introduction: Innate immune cells are important in tumor immunotherapy. Natural killer cells (NKCs) are also categorized as innate immune cells and can control tumor growth and metastatic spread. Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults. NKC-based immunotherapy is a promising treatment strategy against GBM. We previously reported a feeder-free expansion system that yielded large-scale highly purified and cytotoxic NKCs derived from human cord blood (CB). In the present study, we performed comprehensive genomic analyses of NKCs generated from human CB (CBNKCs) as compared those from human peripheral blood (PB) (PBNKCs). Methods: Frozen T cell-free CB mononuclear cells were cultured with recombinant human interleukin (rhIL)-18 and rhIL-2 in anti-NKp46 and anti-CD16 antibody immobilization settings. After 14-day expansion, the total RNA of the CBNKCs or PBNKCs was extracted and transcriptomic analyses was performed to determine their similarities and differences. We also examined CBNKC and PBNKC activity against a GBM cell line. Results: Differential expression gene analysis revealed that some NK activating and inhibitory receptors were significantly downregulated in the CBNKCs compared to PBNKCs. Furthermore, genes related to anti-apoptosis and proliferation were upregulated in the CBNKCs. Enrichment analysis determined that the gene sets related to immune response and cytokines were enriched in the CBNKCs. Gene set enrichment analysis demonstrated that the immune response pathway was upregulated in the CBNKCs. Cytotoxic assays using impedance-based cell analyzer revealed that the CBNKCs enhanced NKC-mediated cytotoxicity on GBM cells as compared to the PBNKCs. Conclusions: We demonstrated the characteristics of human CBNKCs. Cell-based therapy using the CBNKCs is promising for treating GBM.

Clinical Results and Hematologic Predictors of Linear Accelerator-Based Stereotactic Radiosurgery or Fractionated Stereotactic Radiotherapy for Brain Metastasis in Patients Aged 75 Years or Older: A Retrospective Study.

OBJECTIVE: This study aimed to evaluate prognostic factors including pre-radiosurgical blood count in elderly patients (EPs) with brain metastasis (BM) who were treated using linear accelerator (LINAC)-based stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (fSRT) with a micro-multileaf collimator. METHODS: Between January 2011 and November 2021, 101 consecutive EPs with BM were treated by LINAC-based SRS or fSRT using LINAC with a micro-multileaf collimator. EPs were defined as patients aged ≥75 years. RESULTS: The tumors originated from the lungs (n = 90; 89.1%), colon (n = 2; 2.0%), and others (n = 9; 8.8%) in these EPs. The median pretreatment Karnofsky Performance Status was 80 (range, 40-100). The median follow-up time was 10 months (range, 0-76), as was the median survival. The 6-month, 1-year, and 2-year survival in the EP group was 58.3%, 43.2%, and 28.5%, respectively. Freedom from local failure at 6 months and 1 and 2 years was 97%, 95%, and 91.5%, respectively. Freedom from distant failure at 6 months and 1 and 2 years in EPs was 70.6%, 59.4%, and 54.2%, respectively. A high neutrophil/lymphocyte ratio >5.33 was an unfavorable predictor of prognosis for EPs with BMs treated with SRS and fSRT (P < 0.001). In the EPs, the prognostic factors associated with prolonged survival in the Cox proportional hazards model were being female and a good pretreatment Karnofsky Performance Status. CONCLUSIONS: The findings of our study highlight the efficacy of LINAC-based SRS and fSRT with a micro-multileaf collimator in the treatment of EPs with BMs. Neutrophil/lymphocyte ratio can be an important factor in treatment decisions for EPs with BMs.

Thin Calcification Predicts Lipid Component in Carotid Plaque-Relationship Between Lipid Distribution and Thin Calcification.

BACKGROUND: Accurately evaluating plaque characteristics is essential because lesions with lipid-rich plaque put patients at risk of thromboembolic complications from carotid artery stenting. Near-infrared spectroscopy (NIRS) is a diagnostic imaging modality that identifies lipid components from the near-infrared absorption pattern but does not reveal the distribution of calcification. The purpose of this study was to investigate the calcification characteristics of unstable carotid plaques, focusing on relationships between the calcification characteristics revealed by computed tomography angiography and the lipid core distribution derived from NIRS. METHODS: Participants in this retrospective analysis comprised 35 patients (29 men, 6 women; mean age, 76.0 years; range, 52-89 years) who underwent carotid artery stenting in our institute between January 2021 and December 2022. We evaluated the thickness and length of carotid calcifications at the minimal lumen level from preoperative computed tomography angiography and analyzed the relationship with maximum lipid core burden index (max-LCBI) from NIRS. RESULTS: Strong negative linear correlations were observed between the thickness of calcification and max-LCBI at Area (any segment in a target lesion) (r = -0.795, P < 0.001), max-LCBI at minimal lumen area (r = -0.795, P < 0.001) and lipid core burden index (LCBI) at lesion (rate of LCBI in entire plaque lesion) (r = -0.788, P < 0.001), respectively. Significant negative linear correlations were observed between distribution of calcification length and max-LCBI at area (r = -0.429, P = 0.01), max-LCBI at minimal lumen area (r = -0.373, P = 0.027), and LCBI at lesion (r = -0.443, P = 0.008). CONCLUSIONS: Thin and ubiquitous carotid calcification was associated with LCBI values derived from NIRS indicative of carotid lipid plaque distribution, implying the possibility of predicting lesion instability.

Giant skull base periosteal chondroma treated with endonasal endoscopic surgery: illustrative case.

BACKGROUND: Intracranial chondroma is an extremely rare type of tumor composed of mature hyaline cartilaginous tissues. No previous cases of skull base periosteal chondroma have been presented. OBSERVATIONS: A 31-year-old male had progressive memory loss and diminished motivation for the previous 1.5 years. Magnetic resonance imaging revealed a giant tumor with partial calcification arising from the upper clivus and extending to the prepontine cistern. Compression of the brainstem and hypothalamus was significant. Surgery was performed and intentionally limited to an intracapsular resection with endoscopic endonasal surgery (EES), and the brainstem and hypothalamus were successfully decompressed. Pathological examination findings showed a composition of hyaline cartilage with chondrocyte clusters. Genetic testing with next-generation sequencing indicated alternations in IDH1 R132C, KDR Q472H, IDH2 I142L, and TP53 P72R. On the basis of these findings, a diagnosis of periosteal chondroma was made. Postoperatively, complete relief from all symptoms was noted, and MRI one year later showed no evidence of tumor regrowth. LESSONS: This is the first known report of skull base periosteal chondroma. Genetic testing was useful for confirming the diagnosis, and EES was effective for treatment. Should such a tumor show adhesion to an important structure, an intracapsular excision can be beneficial for avoiding complications.

Effect of Sevoflurane Anesthesia on Intraoperative Spikes, High-Frequency Oscillations, and Phase-Amplitude Coupling in MRI-Normal Hippocampus.

INTRODUCTION: The purpose of this study was to determine the effect of sevoflurane anesthesia on spikes, high-frequency oscillations (HFOs), and phase-amplitude coupling using a modulation index in MRI-normal hippocampus, with the aim of evaluating the utility of intraoperative electrocorticography in identifying the epileptogenic hippocampus during sevoflurane administration. METHODS: Eleven patients with intractable temporal lobe epilepsy with a normal hippocampus on MRI underwent extra-operative electrocorticography evaluation. Patients were assigned to the Ictal (+) or Ictal (-) group depending on whether the parahippocampal gyrus was included in the seizure onset zone. Intraoperative electrocorticography was performed under 0.5 and 1.5 minimum alveolar concentration of sevoflurane. The rates of spikes, ripples, fast ripples (FRs), ripples on spikes, FRs on spikes, and MI HFO(3-4 Hz) were evaluated. RESULTS: During the intraoperative electrocorticography procedure, sevoflurane administration was found to significantly increase the rate of spikes, ripples on spikes, fast ripples on spikes, and MI HFO(3-4 Hz) in the Ictal (+) group (P < 0.01). By contrast, the Ictal (-) group exhibited a paradoxical increase in the rate of ripples and fast ripple (P < 0.05). CONCLUSIONS: Our findings indicate that the administration of sevoflurane during intraoperative electrocorticography in patients with MRI-normal hippocampus can lead to a dose-dependent enhancement of epileptic biomarkers (spikes, ripples on spikes, fast ripples on spikes, and MI (HFO 3-4)) in the epileptogenic hippocampus, while paradoxically increasing the rate of ripples and fast ripple in the nonepileptogenic hippocampus. These results have significant implications for the identification of the MRI-normal hippocampus that requires surgical intervention and preservation of the nonepileptogenic hippocampus.

Therapeutic Anti-KIR Antibody of 1-7F9 Attenuates the Antitumor Effects of Expanded and Activated Human Primary Natural Killer Cells on In Vitro Glioblastoma-like Cells and Orthotopic Tumors Derived Therefrom.

Glioblastoma (GBM) is the leading malignant intracranial tumor, where prognosis for which has remained extremely poor for two decades. Immunotherapy has recently drawn attention as a cancer treatment, including for GBM. Natural killer (NK) cells are immune cells that attack cancer cells directly and produce antitumor immunity-related cytokines. The adoptive transfer of expanded and activated NK cells is expected to be a promising GBM immunotherapy. We previously established an efficient expansion method that produced highly purified, activated primary human NK cells, which we designated genuine induced NK cells (GiNKs). The GiNKs demonstrated antitumor effects in vitro and in vivo, which were less affected by blockade of the inhibitory checkpoint receptor programmed death 1 (PD-1). In the present study, we assessed the antitumor effects of GiNKs, both alone and combined with an antibody targeting killer Ig-like receptor 2DLs (KIR2DL1 and DL2/3, both inhibitory checkpoint receptors of NK cells) in vitro and in vivo with U87MG GBM-like cells and the T98G GBM cell line. Impedance-based real-time cell growth assays and apoptosis detection assays revealed that the GiNKs exhibited growth inhibitory effects on U87MG and T98G cells by inducing apoptosis. KIR2DL1 blockade attenuated the growth inhibition of the cell lines in vitro. The intracranial administration of GiNKs prolonged the overall survival of the U87MG-derived orthotopic xenograft brain tumor model. The KIR2DL1 blockade did not enhance the antitumor effects; rather, it attenuated it in the same manner as in the in vitro experiment. GiNK immunotherapy directly administered to the brain could be a promising immunotherapeutic alternative for patients with GBM. Furthermore, KIR2DL1 blockade appeared to require caution when used concomitantly with GiNKs.

Three-dimensional reconstruction imaging by C-arm computed tomography accurately visualizes in-stent neointimal formation in patients with stent-assisted coil embolization.

Background: Stent apposition to the vessel wall and in-stent neointimal formation after stent-assisted coil embolization for intracranial aneurysm are important factors associated with postoperative thromboembolic complications. No assessment methods have been established to depict 3-dimensional (3D) all-round in-stent neointimal formation. Objective: To demonstrate the superiority of Dyna-3D imaging assessment as a modality for all-round ISNF in comparison with conventional two-dimensional digital subtraction angiography (2D-DSA). Methods: Consecutive patients who underwent braided stent-assisted coil embolization for unruptured aneurysm between November 2016 and September 2021 were enrolled. Radiological assessments for stent apposition to the parent vessel after stent deployment and in-stent neointimal formation after 3 months were obtained. Dyna-3D was reconstructed by overlapping a plain image showing stent struts with a rotational DSA image showing the vessel lumen. Reconstructed Dyna-3D images can be rotated to any angle on the screen to evaluate to stent apposition around the vessel and in-stent neointimal formation in 3D, for comparison with 2D-DSA evaluations. Results: Among the 73 patients enrolled, 70 patients (96%) showed complete stent wall apposition on Dyna-3D. Higher intra-rater agreement was confirmed on assessment of in-stent neointimal formation with Dyna-3D (Cohen's κ = 0.811) than with conventional 2D-DSA (Cohen's κ = 0.517). in-stent neointimal formation could not be confirmed on conventional imaging in 9 cases (16%) and on Dyna-3D in 2 cases (3%). The number of in-stent neointimal formations rated as stent wire completely outside the endothelial line was significantly higher with Dyna-3D than with 2D-DSA (p = 0.0001). Conclusion: All-round 3D evaluation by Dyna-3D imaging appears useful for confirming in-stent neointimal formation after braided stent deployment in patients after stent-assisted coil embolization.

CIS deletion by CRISPR/Cas9 enhances human primary natural killer cell functions against allogeneic glioblastoma.

BACKGROUND: Glioblastoma (GBM) is the most common malignant brain tumor and has "immunologically cold" features. Changing GBM to an "immunologically hot" tumor requires a strong trigger that induces initial immune responses in GBM. Allogeneic natural killer cells (NKCs) have gained considerable attention as promising immunotherapeutic tools against cancer, where gene-edited NKCs would result in effective anti-cancer treatment. The present study focused on the immune checkpoint molecule cytokine-inducible SH2-containing protein (CISH, or CIS) as a critical negative regulator in NKCs. METHODS: The GBM tumor environment featured with immunological aspect was analyzed with Cancer immunogram and GlioVis. We generated human primary CIS-deleted NKCs (NK dCIS) using clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) with single guide RNA targeting genome sites on CIS coding exons. The genome-edited NKCs underwent microarray with differential expression analysis and gene set enrichment analysis (GSEA). The anti-GBM activity of the genome-edited NKCs was evaluated by apoptosis induction effects against allogeneic GBM cells and spheroids. We further detected in vivo antitumor effects using xenograft brain tumor mice. RESULTS: We successfully induced human CIS-deleted NKCs (NK dCIS) by combining our specific human NKC expansion method available for clinical application and genome editing technology. CIS gene-specific guide RNA/Cas9 protein complex suppressed CIS expression in the expanded NKCs with high expansion efficacy. Comprehensive gene expression analysis demonstrated increased expression of 265 genes and decreased expression of 86 genes in the NK dCIS. Gene set enrichment analysis revealed that the enriched genes were involved in NKC effector functions. Functional analysis revealed that the NK dCIS had increased interferon (IFN)ɤ and tumor necrosis factor (TNF) production. CIS deletion enhanced NKC-mediated apoptosis induction against allogeneic GBM cells and spheroids. Intracranial administration of the allogeneic NKCs prolonged the overall survival of xenograft brain tumor mice. Furthermore, the NK dCIS extended the overall survival of the mice. CONCLUSION: The findings demonstrated the successful induction of human primary NK dCIS with CRISPR/Cas9 with efficient expansion. CIS deletion enhanced the NKC-mediated anti-tumor effects in allogeneic GBM and could be a promising immunotherapeutic alternative for patients with GBM.

Local administration of shikonin improved the overall survival in orthotopic murine glioblastoma models with temozolomide resistance.

BACKGROUND: Glioblastoma is a type of intracranial malignancy. Shikonin, a Chinese traditional medicine, has been shown to have anti-tumor efficacy toward human glioblastoma cells in vitro. However, shikonin cannot easily cross the blood-brain barrier. To address this issue, we evaluated the anti-tumor effects of direct intracranial infusion of shikonin in in vivo orthotopic syngeneic murine glioblastoma models using C57BL/6 mice. MATERIALS AND METHODS: The cytotoxic effects of shikonin against murine glioblastoma cells, SB28 and CT-2A, were reported resistance to temozolomide, were evaluated using an allophycocyanin-conjugated annexin V and propidium iodide assay with flow cytometry. Impedance-based real-time cell analysis (RTCA) was used to analyze the inhibitory effects of shikonin on growth and proliferation. To evaluate the anti-tumor activity of shikonin in vivo, we used orthotopic syngeneic murine glioblastoma models with SB28 and CT-2A cells. RESULTS: In flow cytometry-based cytotoxic assays, shikonin induced apoptosis. RTCA indicated that shikonin decreased the cell index of murine glioblastoma cells, SB28 and CT-2A, in a dose-dependent manner (p < 0.0001 for both cell lines), while temozolomide did not (p = 0.91 and 0.82, respectively). In murine glioblastoma models, SB28 and CT-2A, direct intracranial infusion of shikonin, as a local chemotherapy, improved the overall survival of mice in a dose-dependent manner compared with control groups (p < 0.0001 and p = 0.02, respectively). While temozolomide did not (p = 0.48 and 0.52, respectively). CONCLUSIONS: The direct intracranial infusion of shikonin has potential as a local therapy for patients with glioblastoma.

Case report: Giant pituitary neuroendocrine tumor presented along with acute visual loss due to pituitary apoplexy after receiving COVID-19 vaccination.

Objective: A case of giant pituitary neuroendocrine tumor presented along with acute visual loss due to pituitary apoplexy after receiving a COVID-19 vaccination is reported. Case presentation: A 45-year-old man was referred for a giant pituitary tumor with bitemporal hemianopsia. A surgical procedure was planned and then delayed due to the COVID-19 outbreak in Japan, with a Pfizer/BioNTech vaccine administered while awaiting surgery. Three days after the second COVID-19 vaccination the patient noted a progressively worsening headache that caused pituitary apoplexy and then a decrease in vision. Emergency surgery was thus performed. Conclusion: Pituitary apoplexy is a rare and life-threatening complication that may occur after undergoing a COVID-19 vaccination.

Extensive Roles and Technical Advances of Middle Meningeal Artery Embolization for Chronic Subdural Hematoma.

Chronic subdural hematoma (CSDH) is a common pathology that typically affects the elderly in Japan, an aging society. Burr-hole irrigation is the standard treatment, but middle meningeal artery (MMA) embolization is a minimally invasive alternative. MMA embolization for CSDH has frequently been reported in recent years, and many technical innovations to improve clinical outcomes have been described. Embolic materials reaching more distally are found to avoid recurrences after MMA embolization. As a result, various studies have described the superiority of embolizing the anterior and posterior branches of the MMA, the advantages of embolic materials reaching beyond the midline, and a high degree of distal penetration using a "sugar rush technique" in which 5% soluble glucose is injected through an intermediate catheter during MMA embolization. Radiographically, reports have described the importance of a "bright falx" sign obtained by infiltrating embolic material beyond the midline and post-embolization enhancement of the dura, capsular membrane, septations, and subdural hematoma fluid as indicators of the spread of embolic materials. This review provides an overview of the current status and future challenges in MMA embolization for CSDH, focusing on technical aspects to improve clinical outcomes.

An efficient feeder-free and chemically-defined expansion strategy for highly purified natural killer cells derived from human cord blood.

Introduction: Natural killer cells (NKCs) are immune cells that can attack cancer cells through the direct recognition of ligands without prior sensitization. Cord blood-derived NKCs (CBNKCs) represent a promising tool for allogenic NKC-based cancer immunotherapy. Efficient NKC expansion and decreased T cell inclusion are crucial for the success of allogeneic NKC-based immunotherapy without inducing graft-versus-host reactions. We previously established an efficient ex vivo expansion system consisting of highly purified-NKCs derived from human peripheral blood. Herein, we evaluated the performance of the NKC expansion system using CB and characterized the expanded populations. Methods: Frozen CB mononuclear cells (CBMCs), with T cells removed, were cultured with recombinant human interleukin (rhIL)-18 and rhIL-2 under conditions where anti-NKp46 and anti-CD16 antibodies were immobilized. Following 7, 14, and 21 days of expansion, the purity, fold-expansion rates of NKCs, and the expression levels of NK activating and inhibitory receptors were assessed. The ability of these NKCs to inhibit the growth of T98G, a glioblastoma (GBM) cell line sensitive to NK activity, was also examined. Results: All expanded T cell-depleted CBMCs were included in over 80%, 98%, and 99% of CD3-CD56+ NKCs at 7, 14, and 21 days of expansion, respectively. The NK activating receptors LFA-1, NKG2D, DNAM-1, NKp30, NKp44, NKp46, FcγRIII and NK inhibitory receptors TIM-3, TIGIT, TACTILE, NKG2A were expressed on the expanded-CBNKCs. Two out of three of the expanded-CBNKCs weakly expressed PD-1, yet gradually expressed PD-1 according to expansion period. One of the three expanded CBNKCs almost lacked PD-1 expression during the expansion period. LAG-3 expression was variable among donors, and no consistent changes were identified during the expansion period. All of the expanded CBNKCs elicited distinct cytotoxicity-mediated growth inhibition on T98G cells. The level of cytotoxicity was gradually decreased based on the prolonged expansion period. Conclusions: Our established feeder-free expansion system yielded large scale highly purified and cytotoxic NKCs derived from human CB. The system provides a stable supply of clinical grade off-the-shelf NKCs and may be feasible for allogeneic NKC-based immunotherapy for cancers, including GBM.

Parenchymal Blood Volume Changes Immediately After Endovascular Thrombectomy Predict Futile Recanalization in Patients with Emergent Large Vessel Occlusion.

OBJECTIVE: More than one third of acute ischemic stroke (AIS) patients do not recover to functional independence even if endovascular thrombectomy (EVT) is performed rapidly and successfully. This suggests that angiographic recanalization does not necessarily lead to tissue reperfusion. Although recognition of reperfusion status after EVT is pivotal for optimal postoperative management, reperfusion imaging assessment immediately after recanalization has not been fully investigated. The present study aimed to evaluate whether reperfusion status based on parenchymal blood volume (PBV) assessment after angiographic recanalization influences infarct growth and functional outcome in patients who have undergone EVT following AIS. METHODS: Seventy-nine patients who underwent successful EVT for AIS were retrospectively analyzed. PBV maps were acquired from flat-panel detector computed tomography (CT) perfusion images before and after angiographic recanalization. Reperfusion status was assessed from PBV values and their changes in regions of interest and collateral score. RESULTS: Post-EVT PBV ratio and ΔPBV ratio, as PBV parameters indicating the degree of reperfusion, were significantly lower in the unfavorable prognosis group (P < 0.01 each). Poor reperfusion on PBV mapping was associated with significantly longer puncture-to-recanalization time, lower collateral score, and higher frequency of infarct growth. Logistic regression analysis identified low collateral score and low ΔPBV ratio as associated with poor prognosis after EVT (odds ratios, 2.48, 3.72; 95% confidence intervals, 1.06-5.81, 1.20-11.53; P = 0.04, 0.02, respectively). CONCLUSIONS: Poor reperfusion in severely hypoperfused territories on PBV mapping immediately after recanalization may predict infarct growth and unfavorable prognosis in patients who undergo EVT following AIS.

Additional Effect of High-output Current and/or High-duty Cycle in Vagus Nerve Stimulation for Adolescent/Adult Intractable Epilepsy.

A vagus nerve stimulation (VNS) device delivers electrical pulses to the vagus nerve at a rhythm defined by the duty cycle. The standard therapeutic range is advocated for an output current of 1.5-2.25 mA and a duty cycle of 10%. As the optimal settings vary from patient to patient, some patients may benefit from additional seizure reduction when stimulated beyond the standard range. A total of 74 patients (15 children aged <12 years and 59 adolescents/adults) who underwent VNS implantation between 2011 and 2020 and who were followed up for at least 2 years were included in this retrospective study. Stimulation parameters exceeding 2.25 mA of output current, 25% of duty cycle, and 0.5625 (2.25 mA × 25%) of current × duty cycle were defined as high stimulation. The proportion achieved an additional seizure reduction of 20%, and the 50% seizure reduction rate at the last follow-up was compared between adolescents/adults and children. Approximately 40% of patients in adolescents/adults treated with high stimulation experienced an additional acute effect, resulting in a 50% or greater reduction in seizures in almost all patients. Moreover, in adolescents/adults, 22.2%-41.9% of the patients were treated with high stimulation, and the responder rate was 69.5%. Conversely, the responder rate in children was 26.7%, significantly worse than that in adolescents/adults, despite higher stimulation. VNS with high-stimulation settings is effective for adolescent and adult patients with intractable epilepsy. Even high stimulation may not be effective in extremely refractory pediatric epilepsy with a high seizure frequency.

Left Temporal Pole Encephalocele With Independent Hippocampal Seizures: Surgical Strategy and Relevance of Epileptic Biomarkers.

SUMMARY: Temporal pole encephalocele (TE) is an increasingly recognized surgically treatable subtype of refractory temporal lobe epilepsy that rarely shows hippocampal involvement. A 27-year-old patient presented with medically intractable epilepsy because of a left temporal pole encephalocele with a normal hippocampus on MRI. Extraoperative electrocorticography showed independent seizure onset with distinct morphology of seizure onset pattern from the temporal pole encephalocele and hippocampus. Additional analysis of ictal and interictal fast ripples revealed different electrophysiological fast ripple profiles in the two seizure onset zones. The patient underwent temporopolar disconnection, eliminating the need for large dural repair and multiple hippocampal transections that helped preserve the intrahippocampal and extrahippocampal memory pathways. Herein, the authors report that independent hippocampal seizures can be observed in patients with temporal pole encephalocele. Features of the ictal and interictal fast ripples can differ depending on the morphology of the seizure onset pattern. The authors suggest that, the interpretation of fast ripples in clinical practice should take seizure onset patterns into consideration.